Intrauterine exposure to tobacco smoke, DNA methylation, and vision disorders in preschool children

学龄前儿童宫内烟草烟雾暴露、DNA 甲基化和视力障碍

基本信息

批准号：
10669723
负责人：
Xuejuan Jiang
金额：
$ 41.25万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10669723
关键词：
African American population Amblyopia Bilateral Biological Biological Assay Biological Markers Biological Process Birth Blood Blood specimen California Chemicals Child Childhood Cigarette Cornea Cotinine Cytosine DNA Methylation Data Development Disease Dose Dryness Early identification Electronic Nicotine Delivery Systems Electronic cigarette Epidemiology Epigenetic Process Etiology Exposure to Eye Eye diseases Fetal Development Fetus Genetic Diseases Genetic study Guanine Health Hyperopia Impairment Individual Inherited Investigation Knowledge Late pregnancy Length Life Light Link Los Angeles Low Birth Weight Infant Measures Mediating Metabolism Methods Methylation Modification Monitor Mothers Motor Neonatal Neonatal Screening Nested Case-Control Study Newborn Infant Nicotine Not Hispanic or Latino Outcome Patient Self-Report Phenotype Play Population Population Heterogeneity Population Study Predisposition Pregnancy Preschool Child Public Health Refractive Errors Research Resources Retinal Diseases Risk Risk Factors Role Scientist Smoke Smoking Source Spottings Strabismus Susceptibility Gene Systems Development Testing Third Pregnancy Trimester Tobacco Tobacco smoke Variant Vision Disorders Visual Acuity aged care providers case control cognitive function early childhood early screening environmental tobacco smoke environmental tobacco smoke exposure fetal genomic locus high risk human old age (65+)improved in vivo inorganic phosphate insight intrauterine environment maternal cigarette smoking multi-ethnic neuron development nicotine replacement novel prevent public health relevance response screening screening program smoking during pregnancy tool treatment response uptake vision development

项目摘要

Project Summary Vision disorders in early childhood, such as strabismus, amblyopia and high hyperopia, can significantly impair the development of visual, motor, and cognitive functions. There is a need for better understanding of their disease etiology which remains mostly unknown and methods for early identification of these disorders, which still remain undetected in many children until their older ages when response to treatment is worse. Maternal smoking during pregnancy (MSP), especially sustained smoking that persisted into third trimester, has been consistently associated with several pediatric vision disorders including hyperopia, strabismus, and bilateral amblyopia, and nicotine is considered as a key chemical responsible for the effects. The broad impact of MSP on multiple vision disorders indicates that disturbance of intrauterine environment and fetal development may play an important role in the development of vision disorders that occur very early in life. However, intrauterine exposure to tobacco smoke or nicotine are not well captured by self-reported MSP, due to under-reporting, exposure to overlooked sources of smoke or nicotine (e.g., environmental tobacco smoke, nicotine replacement therapy), and variation in the uptake and metabolism of tobacco smoke by the mother and in the fetal response to intrauterine disturbance. Objective and reliable measures of biologically effective dose of intrauterine exposure to tobacco smoke or early biological effects of this exposure are needed. There have been major advances in identifying specific genomic loci that are differentially methylated in newborns in response to MSP and accumulating evidence linking alterations to DNA methylation at birth with childhood diseases and outcomes such as low birth weight. These led us to hypothesize that epigenetic changes can alter the development of the vision system in the fetus, leading to the development of vision disorders in early childhood. To test this hypothesis, we propose to conduct a case-control study nested within the Multiethnic Pediatric Eye Disease Study (MEPEDS) and retrieve neonatal dried blood spots (DBSs) that had been collected by the California State’s Genetic Disease Screening Program from MEPEDS children at their birth. Using these biospecimens, we will 1) assess the relationship of cotinine level in DBS and tobacco dosimeter based on DNA methylation marks, in comparison to self-reported MSP, with strabismus, bilateral decreased visual acuity, and hyperopia in 1508 preschool children; and 2) investigate epigenetic susceptibility loci for hyperopia by comparing DNA methylation in neonatal DBS from 508 cases and an equal number of random controls. Findings from this proposed study will have a great impact on assessing population and individual risks from intrauterine exposure to different sources of tobacco smoke, understanding underlying biological mechanisms, early screening of pediatric vision disorders, and preventing adverse impacts of these vision disorders.

项目概要儿童早期的视力障碍，如斜视、弱视和高度远视，会严重损害视力视觉、运动和认知功能的发展需要更好地了解它们。疾病病因学仍然大多未知，以及早期识别这些疾病的方法，在许多儿童中，直到年龄较大时，母亲对治疗的反应较差，才被发现。怀孕期间吸烟（MSP），尤其是持续到妊娠晚期的持续吸烟，已成为与多种儿童视力障碍（包括远视、斜视和双眼视力障碍）始终相关弱视，尼古丁被认为是造成 MSP 影响的关键化学物质。对多种视力障碍的研究表明，宫内环境和胎儿发育的紊乱可能在生命早期发生的视力障碍的发展中发挥着重要作用。由于报告不足，自我报告的 MSP 未能很好地捕捉到接触烟草烟雾或尼古丁的情况，暴露于被忽视的烟雾或尼古丁来源（例如环境中的烟草烟雾、尼古丁替代疗法），以及母亲和孩子对烟草烟雾的吸收和代谢的变化胎儿对宫内紊乱的反应的生物学有效剂量的客观和可靠的测量。宫内暴露于烟草烟雾或这种暴露的早期生物效应是有必要的。在鉴定新生儿差异甲基化的特定基因组位点方面取得了重大进展对 MSP 的反应并积累与出生时和童年时期 DNA 甲基化改变相关的证据疾病和后果，例如低出生体重，这些导致我们与表观遗传变化的斗争。改变胎儿视觉系统的发育，导致早期视力障碍的发展为了检验这一假设，我们建议在多种族的范围内进行病例对照研究。小儿眼病研究 (MEPEDS) 并检索已检测到的新生儿干血斑 (DBS) 加利福尼亚州遗传疾病筛查计划从 MEPEDS 儿童出生时收集的数据。使用这些生物样本，我们将 1) 评估 DBS 中可替宁水平与烟草剂量计的关系根据 DNA 甲基化标记，与自我报告的 MSP 相比，患有斜视的患者双侧下降 1508 名学龄前儿童的视力和远视；2) 调查表观遗传易感性位点通过比较 508 例和同等数量的随机样本中新生儿 DBS 的 DNA 甲基化来了解远视这项拟议研究的结果将对评估人口和个人产生重大影响。子宫内暴露于不同来源烟草烟雾的风险，了解潜在的生物学机制，早期筛查儿科视力障碍，并预防这些视力的不利影响失调。